For example, DNMT3B-mediated DNA hypermethylation, HDAC3-induced histone deacetylation, and BRG1-mediated chromatin remodeling can all significantly downregulate the expression of the transcription factor GATA4 and subsequently cause syndromic and nonsyndromic congenital cardiac defects, such as tetralogy of Fallot and ventricular septal defects 12, 51, 52. Here, GATA4 is linked to ventricular septal defect.